In two scenarios layer based reduction, domain-oriented lumping and their combination are compared with respect to the number of necessary differential equations. The insulin signaling system is used as example system. Insulin concentration is assumed to be constant. The two binding sites on the receptor for Shc and IRS in each case are assumed to be equivalent. 1): All binding site phosphorylations and corresponding bindings are all-or-none interactions. All binding sites on the same molecule can perform graded interactions. 2): All binding site phosphorylations and corresponding bindings are all-or-none interactions. The phosphorylation state of binding sites does not influence phosphorylation of other binding sites on the same molecule. See Additional files 3, 4, 5, 6, 7, 8, for model equations and further explanations.